EULAR recommendations for the management of familial Mediterranean fever

Abstract

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease, but many rheumatologists are not well acquainted with its management. The objective of this report is to produce evidence-based recommendations to guide rheumatologists and other health professionals in the treatment and follow-up of patients with FMF. A multidisciplinary panel, including rheumatologists, internists, paediatricians, a nurse, a methodologist and a patient representative, was assembled. Panellists came from the Eastern Mediterranean area, Europe and North America. A preliminary systematic literature search on the pharmacological treatment of FMF was performed following which the expert group convened to define aims, scope and users of the guidelines and established the need for additional reviews on controversial topics. In a second meeting, recommendations were discussed and refined in light of available evidence. Finally, agreement with the recommendations was obtained from a larger group of experts through a Delphi survey. The level of evidence (LoE) and grade of recommendation (GR) were then incorporated. The final document comprises 18 recommendations, each presented with its degree of agreement (0-10), LoE, GR and rationale. The degree of agreement was greater than 7/10 in all instances. The more controversial statements were those related to follow-up and dose change, for which supporting evidence is limited. A set of widely accepted recommendations for the treatment and monitoring of FMF is presented, supported by the best available evidence and expert opinion. It is believed that these recommendations will be useful in guiding physicians in the care of patients with FMF.

A survey of resistance to colchicine treatment for French patients with familial Mediterranean fever

“…Secondary amyloidosis appearing during the course of FMF was also a leading cause of resistance to colchicine, exclusively observed in the adult population. Physician’s assessment of resistance to colchicine treatment was in accordance with the definition of the French Israeli consortium, “six or more typical attacks in a year or three in 4–6 months with an elevated acute phase response between attacks,” and with the new EULAR recommendations, at least 1 attack/month in a 6-month period with full adherence to colchicine treatment [4, 13]. Another finding is that a number of patients, especially children, received doses of colchicine higher than that recommended and experienced digestive symptoms of intolerance, which could be considered not strictly synonymous with resistance to treatment.…”

“…Indeed, paediatric patients received higher doses than adults and had more side effects but were more fully adherent than adults (48% vs 22%). The international recommendations distinguish low adherence from resistance to colchicine treatment [4, 13], but the practical way to improve the management of this critical issue needs to be determined. New findings have shown that psychological “stress” is sensed by the innate immune system in the brain via the ATP/P2X7R-NLRP3 inflammasome cascade; reversing the activation of this pathway in mice blocked the release of IL-1β (1–3 days after infusion) and produced antidepressant and anxiolytic behavioural effects in non-stressed mice [15].…”

Familial Mediterranean Fever: Recent Developments in Pathogenesis and New Recommendations for Management

“…Recently, with the international collaboration of experienced experts from different countries, the European League Against Rheumatism (EULAR) recommendation set for the management of FMF has been published supported by the best available evidence (17). These recommendations are presented in Table 2.…”

“…If the patient lacks clinical manifestations or subclinical inflammation, genetic diagnosis is not a precise indication to start treatment; however, these patients should be followed-up closely for clinical symptoms or signs of subclinical inflammation (17). In countries where amyloidosis has high frequency, the physician may consider treatment in these patients especially when the patient has homozygous M694V mutation, which is more frequently associated with the development of amyloidosis (9, 21, 71–77).…”

“…In resistant cases, the clinicians should also keep in mind whether the patient is compliant to the therapy (16). Recently, a group of international experts has published the recommendations for the management of FMF to guide physicians taking care of these patients (17). …”